Targeted fluorescence lifetime probes reveal responsive organelle viscosity and membrane fluidity
Targeted fluorescence lifetime probes reveal responsive organelle viscosity and membrane fluidity
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DOI：
10.1371/journal.pone.0211165
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发表时间：
2019-02
期刊：
影响因子：
3.7
通讯作者：
I. E. Steinmark;Arjuna L. James;P. Chung;P. Morton;M. Parsons;C. A. Dreiss;C. Lorenz;G. Yahioglu;K. Suhling
中科院分区：
文献类型：
--
作者：
I. E. Steinmark;Arjuna L. James;P. Chung;P. Morton;M. Parsons;C. A. Dreiss;C. Lorenz;G. Yahioglu;K. Suhling
细胞黏度可以极大地影响生物反应，并与几种人类疾病有关，要直观地观察细胞黏度，唯一的方法就是通过黏度成像。细胞黏度成像已经允许绘制细胞黏度，下一个前沿是细胞器及其微环境的靶向黏度成像。在这里，我们提出了一个荧光分子转子/FLIM框架来成像细胞器粘度和膜流动性，使用化学靶向和细胞器提取相结合。为了证明这一点，我们对线粒体的基质粘度和膜流动性进行了成像，这与人类疾病有关，包括阿尔茨海默病和利氏综合征。我们发现，即使在非病理条件下，两者都是高度动态的，对小的环境和生理变化也有反应。这表明粘度和流动性都不能被认为是固定的，并强调了单细胞，甚至是单细胞器成像的必要性。
The only way to visually observe cellular viscosity, which can greatly influence biological reactions and has been linked to several human diseases, is through viscosity imaging. Imaging cellular viscosity has allowed the mapping of viscosity in cells, and the next frontier is targeted viscosity imaging of organelles and their microenvironments. Here we present a fluorescent molecular rotor/FLIM framework to image both organellar viscosity and membrane fluidity, using a combination of chemical targeting and organelle extraction. For demonstration, we image matrix viscosity and membrane fluidity of mitochondria, which have been linked to human diseases, including Alzheimer’s Disease and Leigh’s syndrome. We find that both are highly dynamic and responsive to small environmental and physiological changes, even under non-pathological conditions. This shows that neither viscosity nor fluidity can be assumed to be fixed and underlines the need for single-cell, and now even single-organelle, imaging.